The Effect of Magnesium Oxide Nanoparticle Supplementation (MgO NPS) on Fetuin-A Gene Expression and Insulin Resistance in Rats with Type 2 Diabetes

Abstract

Background: Fetuin-A is a liver-derived hepatokine and a major contributor to insulin resistance in type 2 diabetes mellitus (T2DM). Individuals with T2DM frequently have low magnesium levels, which are associated with impaired metabolic health; however, standard magnesium supplements have shown variable therapeutic efficacy. Objectives: This study aimed to evaluate the effects of magnesium oxide nanoparticle supplementation (MgO NPS) on hepatic Fetuin-A mRNA expression and insulin resistance parameters in an experimental rat model of T2DM. Methods: A total of 24 male Wistar rats were equally allocated to three experimental groups (n = 8 per group): healthy control (HC), diabetic control (DC), and diabetic rats receiving MgO NPS (DS) at a daily dose of 300 mg/kg by oral gavage for 8 weeks. Diabetes was induced by intraperitoneal administration of nicotinamide (110 mg/kg), followed by streptozotocin (60 mg/kg). Results: Diabetic rats exhibited significantly higher fetuin-A expression and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) values than healthy controls (P < 0.001). MgO NPS significantly reduced both fetuin-A gene expression (1.05 ± 0.10 vs. 1.61 ± 0.16, P < 0.001) and HOMA-IR (1.16 ± 0.16 vs. 1.65 ± 0.25, P = 0.001) in diabetic rats. Conclusions: An 8-week course of MgO NPS significantly ameliorated insulin resistance in diabetic rats, with the downregulation of hepatic Fetuin-A expression as a plausible underlying mechanism. These findings suggest that nano-formulated magnesium may represent a promising candidate for future therapeutic approaches targeting hepatokine-driven insulin resistance in T2DM.